Impact of single and dual neoadjuvant HER2-directed therapy on clinical outcomes among patients with HER2-positive breast cancer (BC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 647-647 ◽  
Author(s):  
Kerry Lynn Reynolds ◽  
Ashmeet Bhatia ◽  
XingXing Cheng ◽  
Barbara Lynn Smith ◽  
Michelle Connolly Specht ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Single Agent ◽  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Complete Response ◽  
Breast Conserving Surgery ◽  
Her2 Positive ◽  
Improve Patient Selection ◽  
The Impact

647 Background: While the addition of trastuzumab to neoadjuvant chemotherapy (CTX) is well established for HER2+ BC, the use of dual agent HER2 blockade in the preoperative setting is not considered standard of care. We conducted a comprehensive systematic review and meta-analysis to evaluate the impact of neoadjuvant dual and single agent HER2 blockade on breast conserving surgery (BCS), pathological complete response (pCR) for estrogen receptor (ER)+ and ER- tumors, and impact of pCR on disease-free survival (DFS) and overall survival (OS) for HER2+ BC. Methods: Based on QUORUM guidelines, MEDLINE and Cochrane Controlled Clinical Trials Register databases were queried to identify eligible trials. Inclusion criteria were prospective, neoadjuvant trials that had at least one arm with HER2 directed therapy, and reported pCR. Pooled relative risk ratios (RRs) and 95% confidence intervals (CIs) were estimated for endpoints using the random effects model. Results: We identified 34 trials (N = 4064). High pCR rates (> 40%) were seen with anthracycline-based CTX and trastuzumab, as well as taxane based CTX alone with dual HER2 blockade. The addition of trastuzumab to CTX did not improve BCS rate (RR 1.40, CI: 0.89-2.22, p=.15), but significantly increased rates of pCR (RR 1.91, CI: 1.38-2.64, p=.0001). Similarly, dual HER2 blockade compared to trastuzumab alone did not improve BCS rate (RR 1.03, CI: 0.77-1.38, p=.84), but significantly increased rates of pCR overall (RR 1.38, CI: 1.24-1.53, p<0.00001), in both ER+ (RR 1.72, CI: 1.14-2.61, p=.01) and ER- subsets (RR 1.91, CI: 1.38-2.64, p=.0001). Higher pCR was associated with improved DFS (RR 2.29, CI: 1.27-4.12, p=.006) and OS (RR 4.61, CI: 1.46-14.56, p=.009). Conclusions: Neither the addition of trastuzumab to CTX, nor the dual-HER2 blockade compared to trastuzumab, improves rates of BCS, but both significantly improve rates of pCR, which is associated with improved DFS and OS. A subgroup of HER2+ BC patients can achieve pCR with dual HER2 blockade without dependence on anthracycline-based therapy. Predictive biomarkers are needed to improve patient selection and personalize the optimal regimen for HER2+ BC.

Neoadjuvant single and dual HER2 blockade among patients with localized HER2-positive breast cancer.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 147-147
Author(s):  
Kerry Lynn Reynolds ◽  
XingXing Cheng ◽  
Ashmeet Bhatia ◽  
Michelle Connolly Specht ◽  
Barbara Lynn Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Meta Analysis ◽  
Single Agent ◽  
Disease Free Survival ◽  
Complete Response ◽  
Breast Conserving Surgery ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Grade 3 ◽  
The Impact

147 Background: Dual neoadjuvant HER2 directed therapy is offered only in a clinical trial setting and is not standard of care, but emerging data suggests targeting multiple mechanisms may be more effective. We conducted a comprehensive systematic review and meta-analysis to evaluate the impact of neoadjuvant dual and single agent HER2 blockade on breast conserving surgery (BCS), and on pathological complete response (pCR) for estrogen receptor (ER)+ and ER- tumors, as well as the impact of pCR on disease-free survival (DFS) and overall survival (OS) for HER2+ breast cancer. Methods: MEDLINE, EMBASE, and Cochrane Controlled Clinical Trials Register databases were queried to identify eligible trials. Inclusion criteria were prospective, neoadjuvant trials that had at least one arm with HER2 directed therapy, and reported pCR. Pooled relative risk ratios (RRs) and p values were estimated for endpoints using the random effects statistical model. Results: We identified 36 trials (N = 4130). High pCR rates (> 40%) were seen with anthracycline-based chemotherapy and trastuzumab alone, and non-anthracycline based dual HER2 blockade. The addition of trastuzumab to chemotherapy did not improve BCS rate (RR 1.40, p = 0.15), but significantly increased rates of pCR (RR 1.91, p = 0.0001). Similarly, dual HER2 blockade compared to trastuzumab alone did not improve BCS rate (RR 1.03, p = 0.84), but significantly increased rates of pCR overall (RR 1.39, p < 0.00001), in both ER+ (RR 1.72, p = 0.01) and ER- subsets (RR 1.91, p = 0.0001), with no increase in grade 3/4 toxicity (RR:1.13, p = 0.16). Dual HER-2 blockade without chemotherapy was associated with pCR in a subset (11.2% - 27%) with minimal toxicity (incidence of grade 3/4 toxicity:1-5%). Higher pCR was associated with improved DFS (RR 2.29, p = 0.006) and OS (RR 4.61, p = 0.009). Conclusions: Neither the addition of trastuzumab to chemotherapy, nor the dual-HER2 blockade compared to trastuzumab, improves rates of BCS. However,both significantly improve rates of pCR, which is associated with improved DFS and OS. Dual HER2 blockade,with endocrine therapy for ER+, could potentially lessen or even obviate the use of chemotherapy.

scholarly journals Impact of hormone receptor status on the efficacy of HER2-targeted treatment

2018 ◽  
Vol 25 (6) ◽  
pp. 687-697 ◽  
Author(s):  
Bin Zhao ◽  
Hong Zhao ◽  
Jiaxin Zhao
Keyword(s):  
Neoadjuvant Therapy ◽  
Hormone Receptor ◽  
Meta Analysis ◽  
Neoadjuvant Treatment ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Complete Response ◽  
Targeted Treatment ◽  
Her2 Positive ◽  
The Impact

The introduction of human epidermal growth factor receptor 2 (HER2)–targeted drugs into routine clinical practice has a dramatic effect on the outlook for patients with HER2-positive breast cancer (BC). However, the association between efficacy of HER2-targeted therapy and hormone receptor (HR) status is still unclear. Here we conducted a meta-analysis of randomized controlled trials (RCTs) to address this issue in both neoadjuvant and adjuvant settings. PubMed and EMBASE were searched from inception to October 2017 for studies involving trastuzumab, lapatinib, pertuzumab, trastuzumab emtansine and neratinib. Efficacy endpoints were pathological complete response (pCR) for neoadjuvant therapy and disease-free survival (DFS) for adjuvant therapy. In neoadjuvant setting, pCR was reported in 7 trials with 2868 subjects. Hormone receptor (HR)–negative women derived substantially greater benefit from HER2-targeted agents than did HR-positive patients (odds ratio (OR), 2.34; 95% confidence interval (CI), 1.99–2.75). Additionally, the impact of HR status on pCR was independent of anti-HER2 agents. In adjuvant setting, DFS was investigated in 7 studies with 12,768 patients. HR-positive patients benefit more from anti-HER2 treatment than did HR-negative subjects (OR, 0.81; 95% CI, 0.74–0.89). Moreover, patients who did not receive any endocrine or anti-HER2 neoadjuvant treatment showed similar outcome but with a smaller effect (OR, 0.88; 95% CI, 0.78–0.99). In summary, compared with HER2-positive/HR-negative subjects, HER2-positive/HR-positive patients achieved greater benefit from HER2-targeted treatment although the efficacy from neoadjuvant therapy was relatively poor.

Biochemotherapy versus chemotherapy for metastatic malignant melanoma: A meta-analysis of the randomised trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8544-8544 ◽  
Author(s):  
N. J. Ives ◽  
R. L. Stowe ◽  
P. Lorigan ◽  
K. Wheatley
Keyword(s):  
Meta Analysis ◽  
Single Agent ◽  
Objective Response ◽  
Interleukin 2 ◽  
Standard Of Care ◽  
Response Rates ◽  
Complete Response ◽  
Metastatic Malignant Melanoma ◽  
Published Data ◽  
The Individual

8544 Background: Metastatic melanoma is associated with a poor survival rate. High response rates have been reported for both chemotherapy and biochemotherapy. To assess whether adding interferon-a (IFN) ± interleukin-2 (IL-2) to chemotherapy is advantageous, a published data meta-analysis of trials of biochemotherapy versus chemotherapy has been performed. Methods: Standard published data meta-analysis methods were used to assess response rates (partial, complete and objective (i.e. partial+complete)) and overall survival (OS), with odds ratios (OR) and 95% confidence intervals (CI) calculated. The only subgroup analysis performed was by type of immunotherapy, with trials divided according to the type of immunotherapy given in the biochemotherapy arm - IFN or IFN+IL-2. Results: Data were available from 18 trials (11 trials of chemotherapy ± IFN and 7 of trials chemotherapy ± IFN+IL-2). Nearly 2500 patients were included in the analysis, with 555 responses and 2,039 deaths observed. There was a clear benefit for biochemotherapy for partial response (OR=0.67, CI=0.54–0.83, p=0.0002), complete response (0.50, 0.35–0.73, p=0.0003) and objective response (0.60, 0.49–0.73, p<0.00001). For objective response, these benefits were significant for both the IFN (0.60, 0.46–0.79, p=0.0002) and IFN+IL2 (0.60, 0.45–0.78, p=0.00002) subgroups. In contrast, there was no benefit on OS (0.99, 0.91–1.08, p=0.9), and there was also evidence of heterogeneity of treatment effect between the individual trials (p=0.006). Conclusions: This meta-analysis shows that biochemotherapy clearly improves response rates, but this does not appear to translate into a survival benefit. Single agent chemotherapy is considered the standard of care for the majority of patients receiving treatment for advanced melanoma outside a clinical trial, and the result of this meta-analysis shows no reason to change this. No significant financial relationships to disclose.

scholarly journals Antitumor activity and efficacy of shorter versus longer duration of anthracycline-taxane neoadjuvant chemotherapy in stage II–III HER2-negative breast cancer: a 10-year, retrospective analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592097008
Author(s):  
Riccardo Lobefaro ◽  
Emma Zattarin ◽  
Federico Nichetti ◽  
Michele Prisciandaro ◽  
Francesca Ligorio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcomes ◽  
Statistical Significance ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Stage Ii ◽  
Specific Patient ◽  
The Impact

Background: Neoadjuvant anthracycline-taxane-based chemotherapy (ChT) is a standard of care treatment option for stage II–III breast cancer (BC) patients. However, the optimal duration of neoadjuvant ChT has been poorly investigated so far. Material and methods: We retrospectively retrieved clinical data of patients with stage II–III human epidermal growth factor receptor 2-negative (HER2–) BC who were treated between October 2007 and January 2018 with neoadjuvant AT (doxorubicin-paclitaxel) for three cycles followed by CMF (cyclophosphamide-methotrexate-5-fluorouracil) for three cycles (cohort A) or with four AT cycles followed by four CMF cycles (cohort B). The aim of our study was to investigate the impact of neoadjuvant ChT duration (cohort A versus cohort B) on pathological complete response (pCR) rates, disease-free survival (DFS) and overall survival (OS). Results: Of 209 HER2– BC patients included, 62 had triple-negative breast cancer (TNBC) and 147 had hormone receptor-positive (HR+) BC. Median age was 48 years (range 30–74 years). A total of 111 patients belonged to cohort A and 98 patients belonged to cohort B. pCR was detected in 29 (13.9%) patients, 25 (40.3%) of whom had TNBC and four (2.7%) had HR+ HER2– BC. Patients achieving pCR had significantly longer DFS and OS, with statistical significance reached only in patients with TNBC. We found no differences between cohort A and cohort B in terms of pCR rates (15.3% versus 12.2%; p = 0.55), DFS ( p = 0.49) or OS ( p = 0.94). The incidence of grade 3/4 adverse events was similar in cohort A versus cohort B as well (22.5% versus 19.4%; p = 0.54). Conclusion: Shorter duration of neoadjuvant anthracycline-taxane ChT was not associated with worse clinical outcomes in patients with stage II–III BC. Prospective studies are needed to evaluate whether the duration of neoadjuvant anthracycline-taxane-based ChT can be reduced in specific patient subgroups without negatively affecting clinical outcomes.

scholarly journals Postoperative chemotherapy with single-agent fluoropyrimidines after resection of colorectal cancer liver metastases: a meta-analysis of randomised trials

ESMO Open ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. e000343 ◽  
Author(s):  
Davide Mauri ◽  
George Zarkavelis ◽  
Panagiotis Filis ◽  
Lampriani Tsali ◽  
Georgia Zafeiri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Benefit ◽  
Meta Analysis ◽  
Single Agent ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Postoperative Chemotherapy ◽  
Colorectal Cancer Liver Metastases

Surgical resection is the only option of cure for patients with metastatic colorectal cancer. Risk of recurrence after metastasectomy is around 75%. Use of adjuvant chemotherapy after metastasectomy is controversial.AimTo address whether adjuvant systemic therapy after colorectal cancer metastasectomy offers any survival benefit compared with surgery alone.MethodsSystematic review of literature and meta-analysis of all available randomised evidence. Relative hazards (RHs) were summarised across trials and heterogeneity was assessed with the Q and I2 statistics.ResultsFive trials were eligible. Three trials, all using single-agent fluoropyrimidine chemotherapy, presented data valuable for analyses. 482 patients were included in the meta-analysis: 238 randomly assigned to receive postoperative chemotherapy and 244 to metastasectomy only. We found no overall survival (OS) benefit with the use of postoperative single-agent fluoropyrimidines compared with surgery alone, even if a trend for benefit was observed (relative hazard (RH)=0.781, 95% CI 0.593 to 1.030, p=0.080). Significant disease-free survival benefit with the use of postoperative chemotherapy was observed (RH=0.645, 95% CI 0.509 to 0.818, p=0.001). No quality of life (QL) data were available. All trials showed accrual delay, two stopped and one recruiting after 10 years. Long follow-up needs were evidenced since OS curves split only after 3.5 years.ConclusionsNo OS benefit was documented from the use of postoperative monochemotherapy. Metastasectomy alone continues to be the standard of care. Combination chemotherapy regimens should be evaluated along with QL assessment in future trials appropriately designed for long-term accrual and follow-up.

scholarly journals Evaluation of Antiviral Therapy Performed after Curative Therapy in Patients with HBV-Related Hepatocellular Carcinoma: An Updated Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Peng Yuan ◽  
Peng Chen ◽  
Yeben Qian
Keyword(s):  
Hepatocellular Carcinoma ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Curative Therapy ◽  
B Virus ◽  
Effect Of Treatment ◽  
Long Term Prognosis ◽  
One Year ◽  
The One ◽  
The Impact

Background.The long-term prognosis after curative therapy for hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) remains unsatisfactory due to the high incidence of recurrence. The effect of treatment with nucleotide analogues (NAs) in patients with HBV-related HCC after curative therapy remains unclear.Objective.To assess the impact of using NAs after curative therapy.Method.A computerized literature search was performed; eligible studies were identified from databases. The pooled risk ratios (RRs) and 95% CIs were calculated using Review Manager 5.3.Result.The meta-analysis included a total of 15 studies with 8060 patients. The one-year and three-year recurrence (one-year recurrence: RR 0.41 [95% CI 0.28 to 0.61];P<0.00001; three-year recurrence: RR 0.63 [95% CI 0.43 to 0.94];P=0.001) and the one-, three-, and five-year overall survival (OS) and disease-free survival (DFS) were significantly better in the treatment group.Conclusion.NAs can reduce the recurrence and improve the prognosis of HBV-related HCC after curative therapy.

scholarly journals Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002057
Author(s):  
Yousef Zakharia ◽  
Robert R McWilliams ◽  
Olivier Rixe ◽  
Joseph Drabick ◽  
Montaser F Shaheen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Programmed Death ◽  
Evaluable Population

BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

scholarly journals Clinicopathological and Prognostic Value of CD24 Expression in Breast Cancer: A Meta-Analysis

2017 ◽  
Vol 32 (2) ◽  
pp. 182-189
Author(s):  
Gao Liu ◽  
Guo-Xing Liu ◽  
Yu Fang ◽  
Zhen-Yu Cao ◽  
Hui-Hui Du ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Pooled Analysis ◽  
Tnm Stage ◽  
Her2 Status ◽  
Relative Risk Ratio ◽  
The Impact

Background A number of studies have been conducted to explore the relationship between CD24 expression and the prognosis of breast cancer; however, the results remain inconsistent. Therefore, we performed this meta-analysis to clarify the impact of CD24 expression on clinicopathological features and prognosis of breast cancer. Methods A comprehensive literature search for relevant studies was performed, and statistical analysis was conducted using Stata software. Results Twenty studies, including 5,179 cases, were included in this meta-analysis. The pooled analysis indicated that CD24 expression was associated with lymph node invasion (odds ratio [OR] = 0.68, for negative vs. positive, 95% confidence interval [95% CI], 0.53-0.87, p = 0.002) and TNM stage (OR = 0.63, for I + II vs. III + IV, 95% CI, 0.49-0.81, p<0.001). The prognosis analysis also suggested CD24 overexpression indicated a poorer 5-year overall survival (OS) rate (relative risk ratio [RR] = 0.93, 95% CI, 0.86-0.99, p = 0.03) and 5-year disease-free survival (DFS) rate (RR = 0.90, 95% CI, 0.83-0.98, p = 0.02). However, CD24 expression had no correlation with tumor size, tumor grade, distance metastasis, estrogen receptor (ER) status, progesterone receptor (PR) status, or HER2 status. Conclusions Our results suggest that higher CD24 expression is significantly associated with lower OS rate, lower DFS rate and some clinicopathological factors such as lymph node invasion and TNM stage. This meta-analysis suggested that CD24 is an efficient prognostic factor in breast cancer.

scholarly journals HER2-enriched subtype and pathological complete response in HER2-positive breast cancer: A systematic review and meta-analysis

2020 ◽  
Vol 84 ◽  
pp. 101965 ◽  
Author(s):  
Francesco Schettini ◽  
Tomás Pascual ◽  
Benedetta Conte ◽  
Nuria Chic ◽  
Fara Brasó-Maristany ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Pathological Complete Response ◽  
Meta Analysis ◽  
Complete Response ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals Microwave Ablation Versus Radiofrequency Ablation for Treatment of Hepatocellular Carcinoma: A Meta-Analysis of Randomized Controlled Trials

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3796
Author(s):  
Antonio Facciorusso ◽  
Mohamed A. Abd El Aziz ◽  
Nicola Tartaglia ◽  
Daryl Ramai ◽  
Babu P. Mohan ◽  
...  
Keyword(s):  
Recurrence Rate ◽  
Event Rate ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Complete Response ◽  
Distant Recurrence ◽  
Adverse Event Rate ◽  
Free Survival ◽  
Randomized Controlled ◽  
Disease Free

There are limited and discordant results on the comparison between microwave ablation (MWA) and radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). This meta-analysis aims to compare the two treatments in terms of efficacy and safety, based on a meta-analysis of randomized-controlled trials (RCTs). A computerized bibliographic search was performed on the main databases throughout August 2020. The primary outcome was the complete response rate, while survival rate (at 1-, 2-, 3-, and 5-year), disease-free survival rate (at 1-, 2-, 3-, and 5-year), local and distant recurrence rate, adverse event rate, and number of treatment sessions were the secondary outcomes. Seven RCTs enrolling 921 patients were included. No difference in terms of complete response between the two treatments was observed (risk ratio (RR) 1.01, 95% CI 0.99–1.02). Survival rates were constantly similar, with RRs ranging from 1.05 (0.96–1.15) at 1 year to 0.91 (0.81–1.03) at 5 years. While local recurrence rate was similar between MWA and RFA (RR 0.70, 0.43–1.14), distant recurrence rate was significantly lower with MWA (RR 0.60, 0.39–0.92). Disease-free survival at 1, 2, and 3 years was similar between the two groups with RR 1.00 (0.96–1.04), 0.94 (0.84–1.06), and 1.06 (0.93–1.21), respectively. On the other hand, RR for disease-free survival at 5 years was significantly in favor of MWA (3.66, 1.32–42.27). Adverse event rate was similar between the two treatments (RR 1.06, 0.48–2.34), with bleeding and hematoma representing the most frequent complications. Our results indicate a similar efficacy and safety profile between the two techniques. MWA seems to decrease the rate of long-term recurrences, but this finding needs to be confirmed in further trials.

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